ArticleJournal of molecular medicine (Berlin, Germany)2012
The calcineurin-NFAT pathway allows for urokinase receptor-mediated beta3 integrin signaling to cause podocyte injury.
Article in Journal of molecular medicine (Berlin, Germany), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 32 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
32 citing papers in PubMed, 47 citations in OpenAlex.
- Serum suPAR levels are modulated by immunosuppressive therapy of minimal change nephrotic syndrome.Pediatric nephrology (Berlin, Germany) · 2014Trial
- Unlocking the therapeutic potential of the NFAT pathway in kidney diseases.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Revisiting nephrin signaling and its specialized effects on the uniquely adaptable podocyte.The Biochemical journal · 2025Review
- Potential biomarkers of recurrent FSGS: a review.BMC nephrology · 2024Review
- Role of biophysics and mechanobiology in podocyte physiology.Nature reviews. Nephrology · 2024Review
- suPAR and WT1 modify the adhesion of podocytes and are related to proteinuria in class IV lupus nephritis.Journal of translational autoimmunity · 2023Article
- Anandamide modulates WNT-5A/BCL-2, IP3/NFATc1, and HMGB1/NF-κB trajectories to protect against mercuric chloride-induced acute kidney injury.Scientific reports · 2023Article
- Perturbations in podocyte transcriptome and biological pathways induced by FSGS associated circulating factors.Annals of translational medicine · 2023Article
- Lipopolysaccharide-induced podocyte injury is regulated by calcineurin/NFAT and TLR4/MyD88/NF-κB signaling pathways through angiopoietin-like protein 4.Genes & diseases · 2022Article
- GAP-43 ameliorates Podocyte injury by decreasing nuclear NFATc1 expression.Biochemistry and biophysics reports · 2021Article
- Old and New Calcineurin Inhibitors in Lupus Nephritis.Journal of clinical medicine · 2021Review
- Exome sequencing in multiple sclerosis families identifies 12 candidate genes and nominates biological pathways for the genesis of disease.PLoS genetics · 2019Article
- MiR-30 family prevents uPAR-ITGB3 signaling activation through calcineurin-NFATC pathway to protect podocytes.Cell death & disease · 2019Article
- Inducible ATF3-NFAT axis aggravates podocyte injury.Journal of molecular medicine (Berlin, Germany) · 2018Article
- Original Research: Potential of urinary nephrin as a biomarker reflecting podocyte dysfunction in various kidney disease models.Experimental biology and medicine (Maywood, N.J.) · 2016Article
- Calcineurin inhibitors cyclosporin A and tacrolimus protect against podocyte injury induced by puromycin aminonucleoside in rodent models.Scientific reports · 2016Article
- Focal segmental glomerular sclerosis: do not overlook the role of immune response.Journal of nephrology · 2016Review
- A CD2AP Mutation Associated with Focal Segmental Glomerulosclerosis in Young Adulthood.Clinical medicine insights. Case reports · 2016Article
- Soluble Urokinase Receptors in Focal Segmental Glomerulosclerosis: A Review on the Scientific Point of View.Journal of immunology research · 2016Review
- MicroRNA-30 family members regulate calcium/calcineurin signaling in podocytes.The Journal of clinical investigation · 2015Article
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
Circulating and podocyte-bound urokinase receptor (uPAR) is a mediator of podocyte injury, proteinuria, and focal segmental glomerulosclerosis (FSGS) allowing pathological activation of the uPAR-β3 integrin signaling axis. Clinically, calcineurin inhibitors (e.g., cyclosporine A, CsA) are known to suppress T cells, yet are also being used to reduce proteinuria in FSGS, suggesting the possibility of signal cross talk between uPAR and calcineurin. Calcineurin is known to facilitate the nuclear translocation of the nuclear factor of activated T cells (NFAT). Accordingly, in vivo conditional NFATc1 activation in podocytes leads to proteinuria in mice, yet the downstream targets of NFAT remain unclear. Here, we show that inducible podocyte-specific expression of constitutively active NFATc1 increased podocyte uPAR expression by binding to the Plaur gene promoter (encoding uPAR) in chromatin immunoprecipitation assays. Pathological uPAR signals in podocytes are independent of T cells and affect cell motility via activation, but not expression, changes of the β3 integrin and can be blocked by CsA, NFAT-siRNA, or the cell-permeable NFAT inhibitor (11R-VIVIT) using rodent models of glomerular disease (LPS; 5/6 nephrectomized rats). Taken together, these findings identify podocyte uPAR as a downstream target of NFAT and provide further insights into the pathogenesis of FSGS.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.